Aerosol drug delivery using helium-oxygen gas mixtures (heliox) is considered in terms of flow physics, atomization, and aerosol mechanics. Theoretical considerations are then related to past studies of the physiological effects of the inhalation of heliox and its potential use as a drug delivery medium. Past clinical trials of heliox investigating this use are reviewed and technical recommendations made for its successful development. It is proposed that improved peripheral lung drug delivery with heliox is highly dependent on proper administration, especially the inclusion of proper reservoir system for the gas.